TY - JOUR
T1 - A platform of C-type lectin-like receptor CLEC-2 for binding O-glycosylated podoplanin and nonglycosylated rhodocytin
AU - Nagae, Masamichi
AU - Morita-Matsumoto, Kana
AU - Kato, Masaki
AU - Kaneko, Mika Kato
AU - Kato, Yukinari
AU - Yamaguchi, Yoshiki
N1 - Funding Information:
We are grateful to the staff of the beamlines at the Photon Factory (Tsukuba, Japan) for providing data collection facilities and support, and Yukishige Ito (RIKEN) and Osamu Kanie (Tokai University) for use of the NMR spectrometer. We also thank Noriko Tanaka (RIKEN) for secretarial assistance and Shinya Hanashima (RIKEN/Osaka University), Yuki Fujii, Yukiko Matsunaga, Yu Kitago, and Junichi Takagi (Osaka University) for helpful discussions and technical assistance. This work was supported in part by Grant-in-aid for Young Scientists (B) 2477011 (to M.N.), Grant for Scientific Research (C) 25460054 (to Y.Y.), Grant 25462242 (to Y.K.), and Grant 26440019 (to M.K.K.) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan; by the Platform for Drug Discovery, Informatics, and Structural Life Science from MEXT of Japan (to Y.K.); and by the Regional Innovation Strategy Support Program from MEXT of Japan (to Y.K.).
Publisher Copyright:
© 2014 Elsevier Ltd. All rights reserved.
PY - 2014/12/2
Y1 - 2014/12/2
N2 - Podoplanin is a transmembrane O-glycoprotein that binds to C-type lectin-like receptor 2 (CLEC-2). The O-glycan-dependent interaction seems to play crucial roles in various biological processes, such as platelet aggregation. Rhodocytin, a snake venom, also binds to CLEC-2 and aggregates platelets in a glycan-independent manner. To elucidate the structural basis of the glycan-dependent and independent interactions, we performed comparative crystallographic studies of podoplanin and rhodocytin in complex with CLEC-2. Both podoplanin and rhodocytin bind to the noncanonical "side" face of CLEC-2. There is a common interaction mode between consecutive acidic residues on the ligands and the same arginine residues on CLEC-2. Other interactions are ligand-specific. Carboxyl groups from the sialic acid residue on podoplanin and from the C terminus of the rhodocytin α subunit interact differently at this "second" binding site on CLEC-2. The unique and versatile binding modes open a way to understand the functional consequences of CLEC-2-ligand interactions.
AB - Podoplanin is a transmembrane O-glycoprotein that binds to C-type lectin-like receptor 2 (CLEC-2). The O-glycan-dependent interaction seems to play crucial roles in various biological processes, such as platelet aggregation. Rhodocytin, a snake venom, also binds to CLEC-2 and aggregates platelets in a glycan-independent manner. To elucidate the structural basis of the glycan-dependent and independent interactions, we performed comparative crystallographic studies of podoplanin and rhodocytin in complex with CLEC-2. Both podoplanin and rhodocytin bind to the noncanonical "side" face of CLEC-2. There is a common interaction mode between consecutive acidic residues on the ligands and the same arginine residues on CLEC-2. Other interactions are ligand-specific. Carboxyl groups from the sialic acid residue on podoplanin and from the C terminus of the rhodocytin α subunit interact differently at this "second" binding site on CLEC-2. The unique and versatile binding modes open a way to understand the functional consequences of CLEC-2-ligand interactions.
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U2 - 10.1016/j.str.2014.09.009
DO - 10.1016/j.str.2014.09.009
M3 - Article
C2 - 25458834
AN - SCOPUS:84914146149
SN - 0969-2126
VL - 22
SP - 1711
EP - 1721
JO - Structure with Folding & design
JF - Structure with Folding & design
IS - 12
ER -